1. Field of the Invention
This invention relates generally to the fields of molecular biology and molecular medicine and more specifically to a novel gene regulatory element and to a cellular factor that binds to the regulatory element.
2. Background Information
Programmed cell death is important for maintaining a steady-state number of cells in a tissue such as skin or intestine that undergoes continual cell renewal. The term "apoptosis" is used to describe a series of morphological events that occurs during the programmed death of cell.
The progression of apoptosis in a cell is regulated by various cellular factors. Apoptosis can be induced by cellular, hormonal or external stimuli to remove unwanted cells from the body. For example, tumor cells and virus-infected cells can be killed via apoptosis by cytolytic T cells following target recognition. Apoptosis also is involved in cell death induced during treatment of a cancer patient by chemotherapy or X-irradiation.
Aberrant regulation of apoptosis can cause a variety of disease states and is associated with various pathological conditions. For example, the death of neurons that occurs in diseases such as Alzheimer's dementia and Parkinson's disease have the hallmarks of apoptosis. Viral infections also can affect the progression of apoptosis in a cell. For example, in the T cell death that is induced by the human immunodeficiency virus, viral infection induces apoptosis. In contrast, during persistent, latent infection of herpes simplex virus, viral infection can inhibit apoptosis through the expression of gene products that block apoptosis.
The bcl-2 gene, which was discovered due to its involvement in a chromosome translocation commonly found in non-Hodgkin's lymphoma, encodes the Bcl-2 protein, which is involved in regulating apoptosis. Low levels of Bcl-2 are associated with increased levels of apoptosis, whereas high levels of Bcl-2 can block cell death. For example, Bcl-2 expression is associated with the survival of long-lived cells such as "memory" lymphocytes, neurons in the brain and in peripheral nerves that control muscle and organ functions and stem cells in the bone marrow, skin and gastrointestinal tract.
In the United States, high levels of Bcl-2 are expected to be present in approximately 50,000 new cases of lymphoma and leukemia each year. High levels of Bcl-2 also are present in essentially all cases of drug-resistant prostate cancer (150,000 cases per year) and colorectal carcinoma (110,000 cases per year), about 80% of nasopharyngeal carcinoma cases and about 70% of breast cancer cases (100,000 cases per year) in the United States. It is likely that inappropriate activation of the bcl-2 gene and resultant high levels of Bcl-2 expression in tumor cells contribute to expansion of a tumor cell population by decreasing the rate of cell death.
The association of proteins such as Bcl-2 with apoptosis in normal cells and in cells associated with various pathological conditions suggests that manipulation of the expression of these proteins can be useful to effect cell death. However, a means for regulating the expression of the genes encoding these proteins has not been available. Thus, a need exists to identify the gene regulatory elements for proteins involved in apoptosis in order to modulate the regulation of programmed cell death. The present invention satisfies this need and provides related advantages as well.